Our program is already conducting a non-intervention study of changes in bone mass and in biochemical markers of bone remodelling in women who are ten years or more post menopause and have not been exposed to postmenopausal hormone replacement therapy [HRT] (AR39657). We are about to begin a controlled clinical trial in the oldest 220 women from this 375 women cohort. That clinical trial (AG 10407) is part of the STOP/IT program and is specifically restricted to persons aged 65 years or older. In this current proposal we will recruit the remaining 155 women into a parallel controlled clinical trial examining the effectiveness of HRT in preventing bone loss from the femoral neck. This will in effect increase our STOP/IT trial size to 375, with age (less that 65, greater that 65) as a new stratum for randomization. This larger trial will allow us to address important additional questions which can not be answered in the smaller trial. Of particular importance is an assessment of whether chronologic age or years postmenopause is a more specific determinant of the "age-related" decline in bone mass and bone strength, and the responsivity to therapies aimed at retarding or reversing this process. To our knowledge this question has not previously been addressed prospectively in an aging female population. The additional power of this larger study will allow us to test the important subgroup hypothesis concerning the potential additive effects of estrogen and progesterone on bone mass. The primary outcome variable of our trial is the effect of HRT bone mass in femoral neck. Secondary outcome variables are the effect of therapy on a)spinal and total body bone mineral, b) selected biochemical markers of bone remodelling and c) some aspects of quality of life in this age group. We will also prospectively monitor the effect of HRT on serum total. HDL and LDL cholesterol, again looking separately at the effects of estrogen and estrogen plus progesterone compared to placebo.